N-methyl-D-aspartate Receptors are Involved in the Quinolinic Acid, but not in the Malonate Pro-oxidative Activity in vitro

Abstract

Oxidative stress plays a significant role in the neurotoxicity of a variety of agents that interact with the N-methyl-D-aspartate (NMDA) receptors. Here we investigated in a comparative way the pro-oxidative effects of quinolinic acid (QA) and malonate, two neurotoxic substances that act through distinct primary molecular mechanisms on the production of thiobarbituric acid reactive species (TBARS) by brain homogenates. In fact, QA is thought to activate directly the NMDA receptor, whereas malonate seems to act primarily by inhibiting oxidative metabolism. The malonate-induced TBARS formation was not modified by cyanide (CN-) or 2,4-dinitrophenol. MK-801 did not reduce basal or malonate induced-TBARS production in fresh tissues preparations. However, in heat-treated preparations a significant effect of MK-801 against basal TBARS production was observed, but not on the malonate induced-TBARS production. QA induced-TBARS production was significantly prevented by MK-801 either in fresh or heat-treated preparations. The antioxidant effect of MK-801 on basal and QA-induced TBARS production increased as the temperatures used to treat S1 were increased. Succinate dehydrogenase (SDH) was inhibited by malonate but not by QA. Malonate was able to chelate iron(II) and the malonate-iron complex(es) is(are) active as measured by its(their) activity on deoxyribose degradation assay. These findings indicate that direct interactions of malonate with NMDA receptors are not involved in malonate pro-oxidative activity in vitro. QA pro-oxidative activity in vitro was related, at least in part, to its capability in stimulate NMDA receptors. Taken together, these findings indicated that malonate pro-oxidative activity in vitro could be attributed to its capability of changing the ratio Fe2+/Fe3+, which is essential to TBARS production.

In vitro Antioxidant Activity of Valeriana officinalis Against Different Neurotoxic Agents

“…The lack of effect of BHT can be attributed to the presence of SDS, which reduces considerably the production of TBARS during color development. In a previous study of our laboratory, TBARS production was about 25-35% higher in tubes that were boiled in the absence of SDS (SDS added after color development) [23]. Fig.…”

“…Thiobarbituric acid reactive substances (TBARS) production was determined as described by Ohkawa et al [22] and Puntel et al [23]. Aliquots of the homogenate (200 ll) from tissues were incubated at 37°C in a water bath in the presence of different concentrations of ethanolic extract of V. officinalis (0-60 lg/ml) and with the respective prooxidant agents.…”

Circulating antibodies to conjugated tryptophan derivatives of the IDO pathway in amyotrophic lateral sclerosis, Alzheimer's, Parkinson's and multiple sclerosis patients

“…There are considerable variations in neuronal apoptosis processes induced by 3-OHkyn and Quina [21]. Quina is an inducer of NF-B pathway, activating c-myc and p53 in rat neostriatum [22] and contributing to N-methyl-d-aspartate receptor production [23,24]. Other tryptophan derivatives may also activate different apoptotic signals, such as Xantha that may interact with the Bcl-2 and caspase 3 signaling pathways.…”

African locust bean (Parkia biglobosa, Jacq Benth) leaf extract affects mitochondrial redox chemistry and inhibits angiotensin-converting enzyme in vitro

“…The ferrous ion chelating activity of extract was evaluated by a standard method [16] with minor changes. The reaction was carried out in Tris-HCL buffer (0.1 M, pH 7.5).…”

“…Quantification of thiobarbituric acid reactive substances (TBARs) production, an index of biological membrane peroxidation, was determined as described by Puntel et al [16]. Briefly, 20 μL of PBE (50-250 μg/mL) and prooxidant agent (100 μm Fe 2+ ) were added to 100 μL of rat liver or brain tissue homogenate in Tris-HCL buffer (10 mM; pH 7.4).…”